Specific Adaptive Mechanisms in Water‐Sodium Regulation in a Desert Rodent Fed With Salty Diets

High-salt diets (HSD) are known to cause renal injury and hypertension in mice, rats, or even humans. Desert rodents have evolved an ability to adapt to water scarcity and concentrated electrolytes in vegetation over a long evolutionary period. However, how the desert rodent species adapt to salty diets remains rarely studied. In this study, we revealed the different adaptive mechanisms in water-sodium regulation using Mongolian gerbils (Meriones unguiculatus) and C57BL/6J mice fed with HSD (containing 4% and 8% NaCl concentrations) as models. The HSD mice showed concentration-dependent reductions in body mass and solute-free water clearance, and increases in total solute excretion, associated with increased nocturnal blood pressure and daily energy expenditure compared with the control mice. In contrast, the HSD gerbils maintained the same body mass and blood pressure as the control gerbils, and adjusted urine osmolality and food intake to achieve water and sodium balance. Transcriptomic and qPCR analysis revealed differential expression of genes related to water and sodium balance, with downregulation of Slc14a2, Nos1, and Corin, and upregulation of Sgk1, Cyp4a14, and Cyp4a10, and upregulation in antioxidative response genes including Gsta1, Gsta2, Gstm3, and Hmgcs2 in mice. However, a small number of differential genes were observed in Mongolian gerbils, with increased Gjb6 and decreased Aqp4 expression related to water-balance regulation, and increased expression of the fibrosis-suppressing gene Grem2. Our study uncovers the unique renal adaptive mechanisms in desert mammals through upregulation of Gjb6 and downregulation of Aqp4 expression for coping with high-salt and arid environments.